Background/Objectives: Instability is one of the main symptoms in patients with vestibular and neurological disorders and therapeutic exercise interventions are increasing its popularity as a way of treatment for those. Additionally, the limits of stability measurement are known to be a good tool for balance evaluation and monitoring of this interventions. The aim of this work is to understand better how a specific protocol provokes changes on this variable and study the characteristics of those who respond and non-respond to it. Methods: A retrospective study was developed with the data of 40 patients treated in the Otorhinolaryngology department in Clínica Universidad de Navarra (Madrid, Spain). Those had an initial reduction in limits of stability, completed the protocol proposed with home-based and hospital-based exercises with frequent limits of stability remeasurement, and assist to the follow-up retest after 1-2 months. Results: A progressive improvement in limits of stability measure was developed through the intervention and partially retained at follow-up visit. Differences were found between responders and non-responders patients. More specifically an initial measure of the limits of stability was able to differentiate those groups with a cut-off data of 56cm2. Conclusions: The protocol proposed was able to induce motor learning in patients included in this study with good retention after 1-2 months. Besides, there is some variability in how patients respond to the treatment. Age and diagnostic should be considered, and an interesting cut-off data for clinal decision making was found.

Rocky Mountain or Brazilian spotted fever, caused by Ricketsia ricketssi, is a fulminant, seasonal, and neglected disease that occurs in focal points of North America and South America. Rapid detection are essential for a better prognosis and survival rate of the infected individual. However, disease diagnosis still faces challenges as the accuracy of many of the available laboratory tests fluctuates. Therefore, this review aimed to identify methods for antibody or antigen detection, its gaps, and evolution over time. A search was conducted to find all studies in the Pubmed database that described antibody or antigen detection for Ricketsia ricketsii infection. Initially, a total of 403 articles were screened. Of these articles, only 19 fulfilled the pre-established inclusion criteria and were selected. Among the different methods applied, the IFA technique was the one most frequently found in the studies. However, it presented varied results such as low specificity using the indirect method. Other techniques, such as ELISA and immunohistochemistry, were also found, although in smaller numbers and with their own limitations. Although some studies showed promising results, there is a pressing need to find new techniques to develop a rapid and effective Ricketsia ricketssi infection diagnosis.

Insect meal as a protein source has been considered a sustainable way to feed animals. H. illucens and T. molitor larvae meal are considered high protein sources for poultry, also presenting considerable amounts of fatty acids, vitamins, and minerals. However, other potential components in insect meal and insect oil have been more studied nowadays. Chitin, lauric acid, and antimicrobial peptides can present antimicrobial and prebiotic functions, indicating that low inclusions of insect meal can beneficially affect broilers` health and immune responses. This systematic review was developed to study the impact of insect products on health parameters of broilers, and a metanalysis was conducted to evaluate the effects on performance. A database was obtained based on a selection of manuscripts from 2016 to January 2023, following the mentioned parameters. There were positive effects of both H. illucens and T. molitor meal or oil products on poultry health status, especially in microbiota population, immune responses, and antimicrobial properties. The average daily gain was greater in broilers fed T. molitor meal compared to H. illucens meal (p = 0.002). The results suggest that low levels of insect meal were suitable for broilers, without result in negative effects on performance, while the insect oil can totally replace soybean oil without negative impacts.

A distinction is made between data rescue (i.e., copying, digitizing and archiving) and data recovery that implies deciphering, interpreting and transforming early instrumental readings and their metadata to obtain high-quality datasets in modern units. This requires a multidisciplinary approach that includes: palaeography and knowledge of Latin and other languages to read the handwritten logs and additional documents; history of science to interpret the original text, data e metadata within the cultural frame of the 17th, 18th and early 19th century; physics and technology to recognize bias of early instruments or calibrations, or to correct for observational bias; astronomy to calculate and transform the original time in canonical hours that started from twilight. The liquid-in-glass thermometer was invented in 1641 and the earliest temperature records started in 1654. Since then, different types of thermometers were invented, based on the thermal expansion of air or selected thermometric liquids with deviation from linearity. Reference points, thermometric scales, calibration methodologies were not comparable, and not always adequately described. Thermometers had various locations and exposures, e.g., indoor, outdoor, on windows, gardens or roofs, facing different directions. Readings were made only one or a few times a day, not necessarily respecting a precise time schedule: this bias is analysed for the most popular combinations of reading times. The time was based on sundials and local Sun, but the hours were counted starting from twilight. In 1789-90 Italy changed system and all cities counted hours from their lower culmination (i.e., local midnight), so that every city had its local time; in 1866, all the Italian cities followed the local time of Rome; in 1893, the whole Italy adopted the present-day system, based on the Coordinated Universal Time and the time zones. In 1873, when the International Meteorological Committee (IMO) was founded, later transformed in World Meteorological Organization (WMO), a standardization of instruments and observational protocols was established, and all data became fully comparable. In the early instrumental period, from 1654 to 1873, the comparison, correction and homogenization of records is quite difficult, mainly because of the scarcity or even absence of metadata. This paper deals about this confused situation, discussing the main problems, but also the methodologies to recognize missing metadata, distinguish indoor from outdoor readings; correct and transform early datasets in unknown or arbitrary units into modern units; finally, in which cases it is possible to reach the quality level required by WMO. The focus is to explain the methodology needed to recover early instrumental records, i.e., the operations that should be performed to interpret, correct, and transform the original raw data into a high-quality dataset of temperature, usable for climate studies.

This review paper explores auditory tactile (AT) synesthesia, a rare neurological condition where sounds evoke tactile sensations. The paper provides a historical overview of the condition and discusses its epidemiology, with a prevalence of less than 1% of the general population. The neurological basis of AT synesthesia is explored, including the role of cross-modal processing and hyperconnectivity within the brain. The paper also describes the phenomenology of the condition, including the range of tactile sensations that can be experienced in response to different sounds. The occurrence of AT synesthesia in the present-day world is discussed, including its relationship to music and art. Various hypotheses surrounding the development and maintenance of AT synesthesia are reviewed, focusing on genetic and environmental factors. The implications for clinical practice are explored, including potential benefits for individuals with sensory processing disorders. Finally, the paper concludes with a discussion of future directions for research in this field, including the need to explore further the underlying neural mechanisms of AT synesthesia and potential therapeutic interventions.

Design for Manufacture and Assembly (DfMA) in architectural, engineering, and construction (AEC) industry is attracting the attention of designers, practitioners, and construction project stakeholders. Digital fabrication (Dfab) and design for additive manufacturing (DfAM) practices are found in current needs for further research and development. The DfMA's conceptual function is to maximize the process efficiency of Dfab and AM building projects. This work reviewed 171 relevant research articles over the past few decades. The concept of DfMA and the fundamentals of DfMA in building and construction were explored. In addition, DfMA procedures associated with Dfab and DfAM, as well as its AM assembly process, were discussed. Lastly, the current machine learning research on DfMA in construction was also highlighted. Large research gaps in the DfMA for Dfab and DfAM can be filled to increase operational efficiency and sustainable practices.

The optimization problem of two or more special-purpose functions of the energy system is subjected to an analysis. Based on experience of our research and general knowledge of partial solutions of energy system optimization at the level of control of production and power energy supply by energy companies in the Czech Republic, a special-purpose (cost) function has been defined. By analysing the special-purpose function, penalty and limitations have been defined. Using the fuzzy logic, a set of suitable solutions for the special-purpose function is accepted. An optimum of the special-purpose function is looked for using the simulated annealing method. The history of electricity consumption is sorted by day and by hour, representing the multidimensional data. When using the cluster analysis, type daytime diagrams of consumption are defined. Type daytime diagrams form prototypes of identified clusters. The so-called self-organizing neural network with Kohonen map attached is used to perform the cluster analysis. The result of our research is presented by an experiment.

The popularity of multiparticulate formulations (MPs) as a paediatric dosage form continues to increase. MPs comprise of multiple small units that are easy-to-swallow. Currently, MPs are commonly manufactured into unit doses that are either swallowed whole or opened prior to administration. While this is an acceptable approach, dosing is envisioned to be optimized with a ‘standard’ paediatric device which can better harness the flexible dosing potential of MPs. We evaluated a novel oral syringe (SympfinyTM) that is being developed as a tool to dispense and administer MPs to children. Forty children, 4-12 years old, received 0.5, 1.2, and 2.0 mL doses of placebo MPs using the oral syringe with spring water or a drink of choice to complete sample intake. Acceptability was recorded as those able to completely swallow the dose and participants also rated dose acceptability on a 5-point scale. The ability to completely swallow the dose decreased as dose volume increased; the smallest dose was completely swallowed by 87.5% (35/40) children, and 69.4% (27/39) of children confirmed their willingness to take the sample as a daily medicine. Larger doses, 1.2 and 2.0 mL, gave values of 55% and 57.5% for the doses completely swallowed and 58.8% and 51.72% for willingness to take the sample as a daily medicine, respectively. Use of a drink of choice showed no increase in swallowability as compared with water. The novel oral syringe being developed is an appropriate device for dispensing doses flexibly and administering neutral tasting MPs directly to the mouth in the lower dose range without the need for a co-administration vehicle in children aged 4-12 years.

As urbanization continues to increase, key conservation areas like World Heritage sites are being altered. This transformation is a cause for concern as it threatens the Outstanding Universal Value of these sites. To address this issue, a research question was formulated: How urban is World Heritage? The research focused on identifying and monitoring urbanization in heritage core zones listed on the World Heritage by tracking changes in built-up areas from 1985 to 2015. The findings revealed that urban developments, including housing, transport infrastructure construction, visitor accommodation facilities, and land conversions, have significantly impacted heritage properties. More than a third (37\%, 426) of the cultural heritage properties reported urban development, with the highest occurrences in Europe, North America, Asia, and the Pacific. Furthermore, these regions also displayed the highest rate of change per year between 1985 and 2015. This indicates the urgent need to identify and monitor the urbanization of World Heritage to preserve their OUV amidst increasing urban development.

The emergence of the coronavirus 19 (COVID-19) has posed a major challenge to healthcare systems worldwide, especially as COVID-19 mutations complicate the development of vaccines and antiviral drugs. Therefore, the search for natural products with broad anti-COVID-19 capabilities is an important option for the prevention and treatment of infectious diseases. Lectins, which are widely recognized as antiviral agents, could contribute to the development of anti-COVID-19 drugs. In this study, we evaluated the binding ability of a total of six lectins, including MVL from Microcystis viridis NIES-102, to the spike protein RBD of the original (wild) COVID-19 and it’s three mutants: alpha, delta, and omicron. As a result, two lectins, MVL from Microcystis viridis NIES-102 and jacalin from Artocarpus altilis, showed distinct binding ability to the RBDs of the four COVID-19 strains. The other lectins (DB1, ConA, PHA-M and CSL3) did not show any binding ability. Although the glycan specificities of the two lectins, MVL and Jacalin, were different, they showed the same affinity for the RBDs of the four COVID-19 strains, i.e., alpha > delta > original > omicron. The verification of glycan-specific inhibition revealed that jacalin binds to RBDs by glycan-specific recognition, whereas MVL binds to RBDs by protein-protein interactions in addition to glycan-specific recognition.

In today's context of rising sea levels and subsiding land topography, coastal flooding is a major concern for coastal areas, both nationally, regionally, and internationally. A detailed understanding of these two phenomena is a prerequisite for effective coastal flood management. The main objective of the present study is to contribute to the understanding of the impact of subsidence and sea-level rise on coastal flooding in Saint-Louis, and in particular the Langue de Barbarie, by producing a vulnerability map of submerged surfaces. To this end, the Synthetic Aperture Radar (SAR) interferometry technique is used to process a time series of Sentinel-1 images and estimate land subsidence in the Saint-Louis and Langue de Barbarie area. Interferometric SAR (InSAR) measurements are merged with RCP 2.6 sea-level rise scenarios to identify predicted flooded areas and provide a flood vulnerability map. At the Langue de Barbarie, topographic subsidence is estimated at between -6.4 and -0.4mm/year. In this study, we show that local land subsidence may increase vulnerability to flooding caused by sea-level rise based on 2100 projections. This may represent an increase in the flood zone in the study area. Based on the RCP 2.6 scenario and the subsidence rates obtained, a significant part of the St. Louis coastline and city would be subject to coastal and fluvial flooding for the years 2040 and 2100. For these dates, 29 to and 36 Km2 of the studied area would be occupied by water. Given this situation, research in Saint-Louis needs to focus on adaptation scenarios to coastal risks, to protect coastal communities and safeguard the city's historical heritage.

Background Cytomegalovirus (CMV) is a major pathogen that cause remarkable rate of morbidity and mortality, especially in immunocompromised patients. It is important to find risk factors associated with CMV viremia. We studied the differences in CMV seropositivity in relation to liver function biomarkers in male and female Saudi population in an attempt to understand the variation in the CMV seroprevalence with sex and find the risk factor to develop liver dysfunction or hepatocellular carcinoma. Material and subjects: The CMV- IgG and IgM were screened in serum samples of 150 non- A-G hepatities patients with elevation of liver profiles (ALT, AST, ALP and GGT) and categorized as males and females. Samples were collected from different general hospitals and polyclinic in KSA from March 2014 to June 2015. A correlation between CMV seropositivity measured with both antibodies and liver enzymes were tested. Receiver operating characteristics (ROC) analysis and multiple regressions were done for the obtained data. Results: Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females. Conclusion:he data discussed above This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old, through counseling on hygiene or possible future vaccination, may lead to a decrease of congenital CMV infections with the concomitant risk of developing liver dysfunction or hepatocellular carcinoma. Keywords: Cytomegalovirus, Alanine transaminase, Aspartate transaminase Alkaline phosphatase, γ-Glutamyltranspeptidase, liver function.

We report an unusual case of Terson's syndrome that resulted in the di-agnosis of a right posterior communicating artery aneurysm. Interest-ingly Terson's syndrome presented with Roth spot resembling features accompanied by third nerve palsy in a patient without any disturbance of consciousness. To our knowledge, the association of Terson's syndrome with third nerve palsy has not been described before in the absence of radiologically diagnosed subarachnoid haemorrhage. We present the case of a 48-year old woman who presented in the De-partment of Emergencies of the University Hospital of Patras with right-sided complete pupil-involving third nerve palsy combined with bilateral Terson's syndrome. More precisely, fundoscopy revealed multi-ple scattered intra- and pre-retinal haemorrhages in both eyes while some retinal haemorrhages had a white-centered pattern resembling Roth spots. Neurological examination revealed no nuchal rigidity or any other neurological signs. The Glasgow coma scale was 15/15. A cerebral computed tomography angiography revealed a 5mm aneurysm of the right posterior communicating artery and the patient underwent a mi-crovascular clipping operation after craniotomy. The significant contribution of the ophthalmological consultation to the appropriate and timely diagnosis and management of a life-threatening condition is highlighted.

Caffeine is a naturally occurring alkaloid found in various plants. It acts as a stimulant, antioxidant, anti-inflammatory and even an aid in pain management, and is found in several over-the-counter medications. This naturally derived bioactive compound is the best-known ingredient in coffee and other beverages, such as tea, soft drinks, and energy drinks, and is the most widely consumed substance worldwide. Therefore, it is extremely important to research the effects of this substance on the human body. With this in mind, caffeine and its derivatives have been extensively studied to evaluate its ability to prevent diseases and exert anti-aging and neuroprotective effects. This review is intended to provide an overview of the effects of caffeine on cancer, cardiovascular, immunological, inflammatory, and neurological diseases, among others. The heavily researched area of caffeine in sports will also be discussed. Finally, recent advances in the development of novel formulations, in the form of dietary supplements of caffeine and nanocarriers, to enhance the bioavailability of caffeine and its beneficial effects will be discussed. On the other hand, caffeine may contribute to elevated blood pressure, anemia, and migraine.

TGF-β signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix remodeling. In this article, we will review how TAK1 activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we will discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development will be critical in designing therapeutics which inhibit tumor progression while bolstering the immune response.

Background: Nephrolithiasis, or kidney stone disease, presents a significant global health burden, with incidence rates and treatment practices varying widely globally. This study aims to discuss the epidemiology, risk factors, treatment modalities, and challenges for nephrolithiasis in the lower half of the World Bank Rank; low and lower-middle-income countries. Methods: A comprehensive literature review was conducted using PubMed for each country on the list, focusing on studies published from January 2000 onwards and reporting data on prevalence, risk factors, treatment practices, and economic implications. Results: Nephrolithiasis represents a significant burden for healthcare systems, with noteworthy geographical variability in prevalence possibly dependent on socioeconomic status and gender. Risk factors include dietary habits, climate, pollution, and infectious diseases. Treatment practices in some regions still rely on open surgery due to limited access to advanced endourological techniques, while other regions demonstrate high proactivity in research. The burden is exacerbated by inadequate healthcare infrastructure and training. Conclusions: Addressing nephrolithiasis in challenging economic circumstances requires targeted interventions, including improved access to modern treatment methods, enhanced training for healthcare professionals, and better socioeconomic and environmental conditions. Future research should focus on region-specific strategies and the development of sustainable healthcare solutions.

The genus Fritillaria belongs to the widely distributed family Liliaceae. The bulbs of Fritillaria ussuriensis and Fritillaria cirrhosa are valuable herbaceous medicinal ingredients. However, they are still used indiscriminately in herbal medicine. Identification and molecular phylogenic analysis of Fritillaria species is therefore required. Here, we report the complete chloroplast (cp) genome sequences of F. ussuriensis and F. cirrhosa. The two Fritillaria cp genomes were 151,524 and 151,083 bp in length, respectively, including a pair of inverted repeat regions (52,678 and 52,156 bp) separated by a large single copy region (81,732 and 81,390 bp) and small single copy region (17,114 and 17,537 bp). A total of 111 genes in F. ussuriensis and 112 in F. cirrhosa comprised 77 protein-coding genes in F. ussuriensis and 78 in F. cirrhosa, 30 tRNA genes, and four rRNA genes. The gene order, content, and orientation of the two Fritillaria cp genomes exhibited the general structure of flowering plants, and were similar to those of other Fritillaria species. Comparison of the six Fritillaria species’ cp genomes indicated seven highly divergent regions in intergenic spacers and in the matK, rpoC1, rpoC2, ycf1, ycf2, ndhD, and ndhF coding regions. We established the position of the six species through phylogenic analysis. The complete chloroplast genome sequences of two Fritillaria species will be useful genomics resources for identification of Fritillaria species and for studying the phylogenetic relationship among Fritillaria species within the Liliaceae family.

TWIST1 is a transcription factor that affects cell behavior during development and cell differentiation. Yet, it is better known for its roles in neoplasia through regulation of cell plasticity. The pathological contributions of TWIST1 in tumor initiation, angiogenesis, invasion, metastasis, and chemo-resistance have been the focus of much research. To-date, the only way to quantitatively measure the abundance of TWIST is by immunoblots. Yet, no bioassay exists that can detect TWIST1 activity. Thus, we present here a TWIST1 cell-based assay that allows measuring the amount of active TWIST1 non-invasively in living cells. The bioassay was characterized against previously described TWIST1 “inhibitors”, as well as by epigenetic modulators of TWIST1 gene expression. Moreover, we tested multiple cell lines, showing that the level of TWIST1 mRNA resembles that of the bioassay. We show that prostate cancer cells (PC3) undergoing EMT, migrate out of 3D-spheroids and have increased TWIST1 activity. This fast and reliable system to detect active TWIST1 in different biological conditions allows a detailed analysis of this factor, as well as it can be used for drug discovery, since TWIST1 is a potential target for cancer chemotherapeutics.

Heterosis of growth traits in economic fish has benefited the production of aquaculture for many years, yet its genetic and molecular basis has been remained obscure. Nowadays, a new germplasm of hybrid Jinhu grouper (Epinephelus fuscoguttatus♀ × E. tukula♂), exhibiting paternal-biased growth heterosis, has provided an excellent model for investigating the potential regulatory mechanisms of heterosis. We integrated transcriptome and methylome to unravel the changes of gene expression, epigenetic modification, and subgenome dominance in Jinhu grouper compared with maternal E. fuscoguttatus. Integration analyses showed that the heterotic hybrids showed lower genomic DNA methylation levels than the purebred parent, and the up-regulated genes were mostly DNA hypomethylation. Furthermore, allele-specific expression (ASE) detected paternal subgenome dominance regulated paternal-biased heterosis, and paternal bias differentially expressed genes (DEGs) were wholly up-regulated in the muscle. Muti-omics results highlighted the role of lipid metabolism, particularly “Fatty acid synthesis”, “EPA biosynthesis”, and “Signaling lipids”, in Jinhu grouper heterosis formation. Coherently, our studies have proved that the eicosapentaenoic acid (EPA) of Jinhu grouper was greater than that of maternal E. fuscoguttatus (8.46% vs 7.46%). Finally, we constructed a potential regulatory network for control of the heterosis formation in Jinhu grouper. Among them, fasn, pparg, dgat1, igf1, pomca, fgf8a, and fgfr4, were identified as key genes. Our results provide new and valuable clues for understanding paternal-biased growth heterosis in Jinhu grouper, taking a significant step towards the molecular basis of heterosis.

Neonatal sepsis is a leading cause of morbidity and mortality in neonates, particularly in low and middle-income countries. The emergence of antimicrobial resistance is a rapidly growing global problem. A significant proportion of the pathogens that commonly cause neonatal sepsis are resistant to multiple antibiotics. Therefore, for the empirical treatment of neonatal sepsis, the repurposing of older antibiotics that are effective against multidrug-resistant pathogens is being investigated. This review aims to provide an overview of current research and experience using the repurposed antibiotics, Colistin and Fosfomycin, for the empirical treatment of neonatal sepsis. Based on current knowledge, Colistin and Fosfomycin may be potentially helpful for the empirical treatment of sepsis in neonates due to their efficacy against a wide range of pathogens and acceptable safety profile.

Winter rapeseed (Brassica rapa) has good chilling and freezing tolerance. INDUCER OF CBF EXPRESSION1 (ICE) plays a crucial role in cold signaling in plant; however, its role in B. rapa remains unclear. In this study, we identified 41 ICE1 homologous genes from 6 widely cultivated Brassica species. These genes exhibited high conservation, with evolutionary complexity between diploid and allotetraploid species. Cold stress induced ICE1 homolog expression, with differences between strong and weak cold-tolerant varieties. Two novel ICE1 paralogs, BrICE1 and BrICE2 were cloned from B. rapa Longyou 6. Subcellular localization assays showed that they localized to the nucleus, and low temperature did not affect their nuclear localization. Overexpression of BrICE1 and BrICE2 increased cold tolerance in transgenic Arabidopsis, and enhanced reactive oxygen species (ROS) scavenging ability. Furthermore, our data demonstrate that overexpression of BrICE1 and BrICE2 inhibited root growth in Arabidopsis, and low temperatures could induce the degradation of BrICE1 and BrICE2 via the 26S-proteasome pathway. In summary, ICE1 ho-mologous genes exhibit complex evolutionary relationships in Brassica species, and are involved in the CBF pathway, and ROS scavenging mechanism in response to cold stress; these regulating mechanisms might be also responsible for balancing the development and cold defense of B. rapa.

Nitrogen fertilization can provide greater nutritional support and mitigate salt stress in the millet crop. The aim of this study was to evaluate the physiological responses and agronomic performance of millet crops subjected to nitrogen fertilization and irrigation water salinity. The study was carried out in a greenhouse, using a completely randomized design in a 5 x 2 factorial scheme, with 4 rep-lications, with five doses of nitrogen (40; 60; 80; 100 and 120 kg ha-1 of N) and two levels of elec-trical conductivity of the irrigation water: 0.3 and 4.0 dS m-1. We concluded that salt stress in-creased leaf sodium levels and had a negative impact on stalk dry mass and panicle dry, leaf gas exchange, mineral element concentrations (K, P and Ca), and water use efficiency. The use of lower salinity water associated with increased nitrogen fertilization provides greater stalk dry mass and panicle dry, photosynthesis, water use efficiency, chlorophyll index, leaf potassium concentration, and biomass production. Salt stress negatively affected transpiration, stomatal conductance, leaf P and Ca levels, and increased leaf sodium levels as nitrogen fertilization increased in millet plants grown under pot conditions. These results can be used to create a strategy to reduce the negative impact of salt stress associated with the nutrition of millet plants, using nitrogen fertilization.

The spread of multidrug-resistant mycobacterium strains requires the development of new approaches to combat diseases caused by these pathogens. For that, photodynamic inactivation (PDI) is a promising approach. In this study, a tricarbocyanine (TCC) is used for the first time as a near-infrared (740 nm) activatable PDI photosensitizer to kill mycobacteria with deeper light penetration. For better targeting, a novel tricarbocyanine dye functionalized with two trehalose units (TCC2Tre) is developed. The photodynamic effect of the conjugate against mycobacteria, including Mycobacterium tuberculosis, is evaluated. Under irradiation, TCC2Tre causes more effective killing of mycobacteria compared to the photosensitizer without trehalose conjugation, with 99.99% dead vegetative cells of M. tuberculosis and M. smegmatis. In addition, effective photoinactivation of dormant forms of M. smegmatis is observed after incubation with TCC2Tre. Mycobacteria treated with TCC2Tre are more sensitive to 740 nm light than the Gram-positive Micrococcus luteus and the Gram-negative Escherichia coli. For the first time, this study demonstrates the possibility of in vitro PDI of mycobacteria including the fast-growing M. smegmatis and the slow-growing M. tuberculosis using near-infrared activatable photosensitizers. These findings are useful for the development of new efficient alternatives to antibiotic therapy.

Background: A challenge in locally advanced, unresectable pancreatic cancer treatment is to achieve both survival benefits and a safe margin-negative resection. There is no robust evidence regarding the treatment of patients with unresectable pancreatic cancer. Methods: We conducted a prospective, single-arm, phase II trial in patients with unresectable pancreatic cancer using the FOLFIRINOX regimen. After completing 4–8 cycles, patients underwent surgical resection when feasible. The primary endpoint was the R0 resection rate. Results: Fifteen patients were enrolled in this study. This study was terminated without reaching the prespecified accrual target due to low accrual rate. A median of six courses of FOLFIRINOX chemotherapy was administered, and a partial response or R0 resection was achieved in 26.7% or 33% of the patients, respectively. Se-vere adverse events due to chemotherapy and major surgical complications were observed in 33.3% and 6.7% of patients, respectively. The median overall survival rate of patients who un-derwent R0 resection or with R1 or unresectable disease was 47.8 months (95% CI, 22.5–73.1) or 14.5 months (95% CI, 11.8–17.2), respectively (P=0.031). Conclusions: Well-selected patients with URLA-PC treated with FOLFIRINOX achieved a relatively high rate of R0 resection and had pro-longed survival. Therefore, induction FOLFIRINOX is feasible and well-tolerated for locally ad-vanced, initially unresectable pancreatic cancer, and may be effective in facilitating R0 resection and prolonging survival. This should be further assessed in future randomized multicenter trials.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butylhydroperoxide(TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM+10% FBS for 24 hours and pretreated with different concentrations of MDHB or N-acetyl-L-cysteine (NAC) for 4 hours prior to the addition of 40 μM TBHP for 24 hours. Cell viability was analyzed using the methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rate. The 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells

Intermittent fasting (IF) has been indicated as a valuable alternative to the classical caloric restriction dietary regimen for lowering body weight and preventing obesity-related complications such as metabolic syndrome and type II diabetes. However, is it effective? In this review article, we analyzed over 50 clinical studies in which IF, conducted by alternate day fasting (ADF) or time-restricted feeding (TRF), was compared with the caloric restriction approach. We evaluated the different roles of IF in treating and preventing human disorders such as metabolic syndrome, type II diabetes, and some types of cancer, as well as the usefulness of IF in reducing body weight and cardiovascular risk factors such as hypertension. Furthermore, we explored the cellular pathway targeted by IF to exert their beneficial effects by activating effector proteins that modulate cell functions and resistance to oxidative stress. In contrast, we investigated the concerns for human health related to the adoption of IF dietary regimen, highlighting the profound debate on weight loss regimens. We have examined and compared several clinical trials to formulate an updated conception regarding IF and its therapeutic potential.

Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs by a pharmacokinetics–pharmacodynamics (PK–PD) approach. Five dogs received an intravenous bolus dose of FMX (40 mg/kg). Serum FMX concentrations were evaluated using high-performance liquid chromatography-tandem mass spectrometry, and PK indices were determined based on non-compartmental model. The cumulative fraction of response (CFR) was calculated based on the distribution of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. As the results, the dosage regimens of 40 mg/kg q8h and q6h were estimated to achieve a CFR of >90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. In contrast, all regimens exhibited a CFR of <80% for ESBL-producing Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX q8h and q6h can be a non-carbapenem treatment for dogs infected with ESBL-producing isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those infected with ESBL-producing Enterobacter cloacae.

Additive manufacturing (AM) of high strength Al alloys promises to enhance the performance of critical components related to various aerospace and automotive applications. The key advantage of AM is its ability to generate lightweight, robust, and complex shapes. However, the characteristics of the as-built parts may represent an obstacle to satisfy the part quality requirements. The current study investigates the influence of selective laser melting (SLM) process parameters on the quality of parts fabricated from different Al alloys. A design of experiment (DOE) is used to analyze relative density, porosity, surface roughness, and dimensional accuracy according to the interaction effect between the SLM process parameters. The results show a range of energy densities and SLM process parameters for the AlSi10Mg and Al6061 alloys needed to achieve “optimum” values for each performance characteristic. A process map is developed for each material by combining the optimized range of SLM process parameters for each characteristic to ensure good quality of the as-built parts. The second part of this study investigates the effect of SLM process parameters on the microstructure and mechanical properties of the same Al alloys. This comprehensive study is also aimed at reducing the amount of post-processing needed.

The evaluation of nanostructured biomaterials and medicines is associated with 2D cultures that provide insight into the biological mechanisms at the molecular level, while critical aspects of the tumor microenvironment (TME) are provided by the study of animal xenograft models. More realistic models that can histologically reproduce human tumors are provided by tissue engineering methodologies of co-culturing cells of varied phenotypes, to provide 3D tumor spheroids that recapitulate the dynamic TME in 3D matrices. The novel approaches of 3D tumor models are combined with tumor tissue engineering (TTE) scaffolds including hydrogels, bioprinted materials, decellularized tissues, fibrous and nanostructured matrices. This review focuses on the use of nanostructured materials in cancer therapy and regeneration, and the development of realistic models for studying TME molecular and immune characteristics. Tissue regeneration is an important aspect of TTE scaffolds for restoring the normal function of the tissues, while providing cancer treatment. Thus, this article reports recent advancements on the development of 3D TTE models for antitumor drug screening, studying of tumor metastasis, and tissue regeneration. Also, this review identifies the great opportunities of 3D TTE scaffolds in the evaluation of the immunological mechanisms and processes involved in the application of immunotherapies.

Globally, over the past several months millions of persons contracted the coronavirus disease 2019 (COVID-19) resulting in significant mortality. Health care systems are negatively impacted including the care of individuals with cancers and other chronic diseases such as chronic active hepatitis, cirrhosis and hepatocellular carcinoma. There are various probable pathogenic mechanisms that have been presented to account for liver injury in COVID-19 patients such as hepatotoxicity cause by therapeutic drugs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the bile duct cells and hepatocytes, hypoxia and systemic inflammatory response. Liver biochemistry tests such as AST, ALT, GGT and ALP are deranged in COVID-19 patients with liver injury. Hepatocellular damage results in the elevation of serum AST and ALT levels in early onset disease while a cholestatic pattern that develops as the disease progress causes higher levels of ALP, GGT, direct and total bilirubin. These liver biochemistry tests are prognostic markers of disease severity and should be carefully monitored in COVID-19 patients. We conducted a systematic review of abnormal liver biochemistry tests in COVID-19 and the possible pathogenesis involved. Significant findings regarding the severity, hepatocellular pattern, incidence and related clinical outcomes in COVID-19 patients are highlighted.

Food tourism, an increasingly vital sector within tourism, significantly impacts both the economic vitality and cultural enrichment of tourist destinations. It attracts a diverse range of visitors, both local and international, while enhancing appreciation for regional culinary traditions. This study employs scenario planning to uncover pivotal factors influencing food tourism in rural Iran. Methodologically, it combines objective-driven, descriptive-analytical approaches with future studies methodologies. Data sourced from literature reviews, field studies, and expert surveys, facilitated by MICMAC and ScenarioWizard software, identified six key drivers: promotional activities, pricing, food quality, infrastructure, government support, and investment. The study forecasts future scenarios based on these drivers, revealing optimistic, stagnant, and crisis condi-tions impacting food tourism development. To achieve favorable outcomes, prioritizing these drivers is essential, ensuring sustainable growth and seizing tourism opportunities in rural Iran. This research contributes by systematically analyzing critical factors driving food tourism using scenario-based insights, essential for sector longevity and prosperity.

Currently, historical areas in China are facing issues of color authenticity and excessive commercialization. Colors, as an important element of historical areas, reflect their history and culture. However, there are some flaws in the existing research methods, so a more scientific and systematic method is needed to obtain accurate and objective color visualization results to promote the sustainable development of historical areas. In order to explore the methods and applications of visualizing the environmental color genes of historical areas, Shiquan Street in Suzhou, China was taken as the research object, ArcGIS 10.5 was used to obtain the street veiw photo samples, Matlab was used to summarize the architectural colors of the historical areas, and K-means clustering was used to generate the central color card of the historical areas, thus completing the color visualization of the historical areas, followed by further searching for the color patterns and central colors, so as to explore the strategies for sustainable development of historical areas. The various quantified color models of historical areas can explore the regional uniqueness and color locality of historical areas, which avoids problems such as homogenization of block colors, unclear styles and features, and excessive proportion of commercial colors caused by poor color guidance and control in the design related to historical areas, providing approaches to the research on the harmonious unity of environmental colors and features related to historical areas.

Driven by industrialization and urbanization, urban air pollution can increase respiratory, heart, and cerebrovascular diseases, and thus mortality rates; as such, it is necessary to improve air quality through the consideration of individual pollutants and emissions sources. In South Korea, national and local governments have installed urban and roadside air quality monitoring systems. However, stations are lacking outside metropolitan regions, and roadside stations are sparsely distributed, limiting comparisons of pollutant concentrations with vehicle traffic and floating population levels. Local governments have begun using mobile laboratories (MLs) to supplement the fixed measurement network and investigate road pollution source characteristics based on their spatiotemporal distribution; however, the collected data cannot be used effectively if they are not visualized. Here, we propose a method to collect and visualize global information system (GIS)-based air quality data overlayed with environmental variables to support air quality management measures. Spatiotemporal analyses of ML-derived data from Bucheon, Korea, confirmed that particulate and gaseous pollutant concentrations were high during typical commuting hours, at intersections, and at a specially managed road. During commuting hours, the maximum PM10 concentration reached 200.7 µg/m³ in the Nae-dong, Gyeongin-ro, and Ojeong-dong ready-mix concrete complex areas, and the maximum PM_2.5 concentration was 161.7 µg/m³. The maximum NOx, NO₂, and NO levels of 1.34 ppm, 0.18 ppm, and 1.18 ppm, respectively, were also detected during commuting hours. These findings support the need for targeted management of air pollution in this region, and highlight the benefit of comprehensively comparing road levels, driving speed, and traffic levels when identifying hotspots of air pollution. Such analyses will contribute to the development of air quality management measures customized to regional characteristics.

Sustainable biomass production has significant potential for mitigating greenhouse gas emissions and is a promising alternative for the production of eco-friendly biofuels, biochemicals, and carbonaceous materials for biological, energetic, and environmental applications. Biomass from agroforestry and agricultural wastes is the richest natural carbon source and a sustainable option for woody biomass from a circular economic perspective. Portugal has several residues and by-products of agriculture, food processing, and forestry origin, and has a high availability of residual biomass. Portugal intends to reduce its dependence on energy imports and the use of fossil fuels, thereby increasing its economic performance while using biomass waste to produce high-value-added products. In this context, this review aims to explore the potential of agri-food wastes obtained from Portuguese industries via thermochemical conversion technologies as a promising sustainable alternative to woody biomass for the development of eco-friendly biofuels, biochemicals, and high-value carbonaceous materials and their applications. This strategy based on the circular bioeconomy concept can contribute to reducing the dependence on fossil fuels and minimising greenhouse gas emissions while meeting the demands of the growing population and providing a sustainable waste management solution.

Optical switches are a key element in modern network communications. We present the results of experimental verification of a new theoretical concept proposed earlier for a full-optical wavelength-selective dual-channel switch based on the photonic hook effect, which is free from using any micro-mechanical devices or nonlinear materials. A large-scale laboratory prototype of such a device based on an off-axis Wood zone plate is considered and its main parameters in the millimeter wavelength range are investigated On the basis of the experiments, we show that the optical isolation of switched channels for a switch based on an off-axis zone plate can achieve 15 dB at a frequency difference of 25 GHz in frequency range from 93 to 136 GHz. Given the scaling, these results can be transferred to another range, including the optical one.

Fibre reinforced concrete (FRC) has become an alternative for structural applications due its outstanding mechanical properties. The appearance of new types of fibres and the fibre cocktails that can be configured mixing them has created FRC that clearly exceed the minimum mechanical properties required in the standards. Consequently, in order to take full advantage of the contribution of the fibres in construction projects, it is of great interest to have constitutive models that simulate the behaviour of the materials. This study aimed to simulate the fracture behaviour of five types of FRC, three with steel hooked fibres, one with a combination of two types of steel fibres and one with a combination of polyolefin fibres and two types of steel fibres, by means of an inverse analysis based on the cohesive crack approach. The results of the numerical simulations defined the softening functions of each FRC formulation and have pointed out the synergies that are created through use of fibre cocktails. The information obtained might suppose a remarkable advance for designers using high-performance FRC in structural elements.

Based on 2010, 2013 and 2015 CGSS data, the impact of Internet use and social capital on the income gap among farmers in the past five years is assessed at three time points using the OLS method and a quantile regression method. The study finds that (1) the income gap among farmers increases continuously in the five-year period, while Internet use plays a positive impact on farmers’ income growth in all five quartiles; the coefficient differences are all significantly negative, indicating that Internet use plays a positive role in alleviating the income gap between high-income and low-income farmer subgroups, and (2) social capital plays a positive role in moderating the income gap among farmers and that Internet use by farmers expands the boundary of social capital, which in turn increases the income level of and alleviates the income gap among farmers.

The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the artificial regulation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. First, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan-qPCR assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.

Dengue is one of the life-threatening common neglected tropical diseases of the world, yet to develop any therapeutic for its treatment and prevention. Although there is a licensed vaccine reported, but becomes less efficacious due to the presence of multiple serovars of the dengue virus (DENV). Thus, an efficacious dengue vaccine potent to work against all the serovars is very crucial and time-demanding. Here we used a comprehensive hierarchical reverse vaccinology approach to design an epitope-based vaccine, targeted against multiple serovars of the DENV. Conservancy and population coverage analysis of the promiscuous epitopes revealed the robust immune response against multiple serovars of the DENV and various ethnicities. Final vaccine constructs comprising of B and T-cell epitopes, Universal pan-HLA DR or PADRE (AKFVAAWTLKAAA) sequence, and an adjuvant (β-defensin) at N-terminal of the construct with suitable linkers. Physiochemical properties and secondary structure profiling of the vaccine protein secured its hydrophilic, thermostable, and other structural nature. Molecular docking analysis indicates the deep binding of the proposed vaccine in the binding groove of the human immune TLR4 receptor present on the dendritic cell. In addition, disulfide engineering was coped to extend its stability. Furthermore, molecular dynamics simulation of the modeled vaccine-TLR8 complex showed minimum deformability. Finally, in silico cloning approach of the vaccine construct within an expression vector (pET28a+) assure good expression. Proposed vaccine may give novel insights for treatment of dengue patients.

This paper introduces a surrogate model to reduce the huge computational load in the process of simulation-optimization and uncertainty analysis. First, the groundwater numerical simulation model was established, calibrated and verified in the northeast of Hetao Plain. Second, two surrogate models of simulation model were established using support vector regression (SVR) method, one (surrogate model A, SMA) was used to describe the corresponding relationship between the pumping rate and average groundwater table drawdown, and another (surrogate model B, SMB) was used to express the corresponding relationship between the hydrogeological parameter values and average groundwater table drawdown. Third, an optimization model was established to search an optimal groundwater exploitation scheme using the maximum total pumping rate as objective function and the limitative average groundwater table drawdown as constraint condition, the SMA was invoked by the optimization model for obtaining the optimal groundwater exploitation scheme. Finally, the SMB was invoked in the process of uncertainty analysis for assessing the reliability of optimal groundwater exploitation scheme. Results show that the relative error and root mean square error between simulation model and the two surrogate models are both less than 5%, which is a high approximation accuracy. The SVR surrogate model developed in this study could not only considerably reduce the computational load, but also maintain high computational accuracy. The optimal total pumping rate is 7947 m3/d and the reliability of optimal scheme is 40.21%. This can thus provide an effective method for identifying an optimal groundwater exploitation scheme and assessing the reliability of scheme quickly and accurately.

We investigate alternative candidates to dark energy that can explain the current state of the universe in the framework of the generalized teleparallel theory of gravity f(T ) where T denotes the torsion scalar. To achieve this, we carried out a series of reconstruction taking into account to the ordinary and entropy-corrected versions of the holographic and new agegraphic dark energy models. These models used as alternative to dark energy in the literature in order describe the current state of our universe. It is remarked that the models reconstructed indicates behaviors like phantom or quintessence models. Furthermore, we also generated the EoS parameters associated to entropy-corrected models and we observed a transition phase between quintessence state and phantom state as showed by recent observational data. We also investigated on the stability theses models and we created the {r − s}. The behavior of certains physical parameters as speed of sound and the Statefinder parameters are compatible with current observational data.

Introduction: An epidemic of Coronavirus Disease 2019 (COVID-19) begun in December 2019 in China, causing a Public Health Emergency of International Concern. Among raised questions, clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews have been published on this matter. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies, and also case reports, were included and analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Results: 660 articles were retrieved (1/1/2020-2/23/2020). After screening by abstract/title, 27 articles were selected for full-text assessment. Of them, 19 were finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 40.8-74.4%) and dyspnea (45.6%, 10.9-80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), with 32.8% presenting acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock and 13.9% (95%CI 6.2-21.5%) of hospitalized patients with fatal outcomes (case fatality rate, CFR).Conclusion: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and this group was associated with a CFR of over 13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure, and facilities to treat severe COVID-19.

Blueberries are rich in a variety of functional substances and have high nutritional and health values, but they are not resistant to decline during fresh storage. Here, the effects of six Bacillus species on storage quality of, and antioxidant levels in, the southern highbush blueberry ‘O'Neal’ fruit were investigated. Bacillus treatments reduced the fruit decay rate, slowed fruit quality decline, inhibited malondialdehyde accumulation, and increased superoxide dismutase and peroxidase activity levels. Bacillus altitudinis Y-14 had the best effect overall. Further, the effects of 1-methylcyclopropene (1-MCP), B. altitudinis Y-14, and 1-MCP+B. altitudinis Y-14 treatments on the storage quality and antioxidant of rabbiteye blueberry ‘Brightwell’ fruit were investigated, and each treatment effectively reduced the decay rate and weight loss of fruit. When stored for 25 days, the decay rate of the 1-MCP+B. altitudinis Y-14 group was only 8.33%, significantly lower than that of the control. The three treatments delayed the fruit quality decline, inhibited malondialdehyde accumulation, and increased superoxide dismutase and peroxidase activity levels. The 1-MCP+B. altitudinis Y-14 treatment had the best effect. Thus, the combined 1-MCP and B. altitudinis Y-14 treatment may be an effective way to improve the storage quality and extend the storage period of blueberries.

Bovine respiratory disease (BRD) inflicts significant losses in cattle farming worldwide and is caused by the co-occurrence of various infectious agents which is often compounded by envi-ronmental factors. It is well known that microorganisms of the Mollicutes class are responsible for respiratory disorders in cattle, including BRD. This review highlights the current role of these microorganisms, in particular Mycoplasma bovis and Mycoplasma dispar, in the aetiology of this disease complex, which has recently shifted towards a primary or predominant cause of the disease.

Peptide/Histidine Transporter PHT1 (SLC15A4) is expressed in lysosomal membranes of immune cells where it plays an important role in metabolic and inflammatory signaling. PHT1 is an H+-coupled/histidine symporter that can transport a broad range of oligopeptides, including a variety of bacterial-derived peptides. Moreover, it enables the scaffolding of various metabolic signaling molecules and interacts with key regulatory elements of the immune response. Therefore, it is not surprising that PHT1 is associated with the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Unfortunately, the pharmacological development of PHT1 has been hampered by the lack of appropriate transport assays. With the aim to address this shortcoming, a novel transport assay based on solid supported membrane-based electrophysiology (SSME) is presented. Key findings of the present SSME studies include the first recordings of electrophysiological properties, a pH dependence analysis, an assessment of PHT1 substrate selectivity, as well as the transport kinetics of the identified substrates. In contrast to previous works, PHT1 is studied its native lysosomal environment. Moreover, observed substrate selectivity is validated by molecular docking. Overall, this new SSME-based assay is expected to contribute to unlock the pharmacological potential of PHT1 and to deepen the understanding of its functional properties.

Extension of a derivation on a universally reversible JC-algebra A⊆B(H)_{sa} to the C*-algebra [A] generated by A in B(H) was studied by Upmier [20, Theorem 2.5]. In this article we study the extension of a Jordan derivation on a universally JC-algebra A to its universal enveloping real and complex C*-algebras R and U, respectively. Also, we establish the relationship between local derivations (resp., 2-local derivations, weak local derivations, weak-2-local derivations) of a universally JC-algebra A and the corresponding maps on its universal enveloping real and complex C*-algebras R and A, respectively.

Wood and plants are made of fibers which contain, in addition to cellulose, lignin and hemicelluloses. Xylan and galactoglucomannan are the dominant secondary cell wall hemicelluloses. Besides fibers’ traditional use in textile and paper industries, the fibers are important materials for the biorefinery industry and for developing biocomposites. In the former context, renewable lignocellulosic biomass is used as feedstock to sustainably produce fuels, chemicals, and polymers. On the other hand, in relation to composites, cellulose fibers which are anisotropic play an important reinforcing role in fiber-matrix interactions. However, for these and other applications, structural analysis of the fibers is important and among many analytical techniques used, Raman spectroscopy is one of the methods. However, given the structural similarity between hemicelluloses and cellulose, many of their Raman contributions overlap. While the wavenumber positions corresponding to the Raman contributions of cellulose, hemicelluloses, and lignin are known, extent to which overlapping features of hemicellulose modify the spectrum of cellulose is not yet fully understood. The present investigation focuses on this aspect by using xylan as one of the hemicelluloses. As a model system, samples with various mass ratios of microcrystalline cellulose (cotton) and xylan (birch wood) were prepared and analyzed by FT-Raman spectroscopy. The findings were then applied to interpret Raman spectra of selected xylan containing delignified plant fibers. It is hoped that insights gained would lead to better interpretation of the spectra of natural and treated plant materials.

Balance requires constant adjustments in muscle activation to attain force steadiness. Creating appropriate training can be challenging. The purpose of this study was to examine the effects of two weeks front squat instability training using a water-filled training tube on force steadiness during an instability challenge. Control (CON, n= 13) and experimental (EXP, n=17) subjects completed pre and post testing for EMG variability by completing one set of 10 repetitions with a stable and unstable training tube. Electrodes were placed bilaterally on the anterior deltoid, paraspinal and vastus lateralis muscles. CON subjects completed 2 weeks of training using a stable training tube, while EXP subjects trained with a water-filled instability tube. EMG data were integrated for each contraction and force steadiness computed using the natural log of coefficient of variation. CON results showed no changes in force steadiness for any condition. EXP showed significant reductions in EMG activation variability across all muscles. These results indicate a significant training effect in reducing muscle activation variability in subjects training with a water-filled instability training device. Improvements seen in these healthy subjects supports development of training implements for a more clinical population to help improve force steadiness.

The nonlocality (superdiffusion) of turbulence is expressed in the empiric Richardson t3 scaling law for the mean square of the mutual separation of a pair of particles in a fluid or gaseous medium. The development of the theory of nonlocality of various processes in physics and other sciences based on the concept of Lévy flights resulted in the idea of Shlesinger and colleagues about the possibility of describing the nonlocality of turbulence using a linear integro-differential equation with a slowly falling kernel. The close approach developed by us made it possible to establish the closeness of the superdiffusion parameter of plasma density fluctuations moving across a strong magnetic field in a tokamak to the Richardson law. In this paper, we show the possibility of a universal description of the characteristics of nonlocality of transfer in a stochastic medium (including turbulence of gases and fluids) using the Biberman-Holstein approach to the transfer of excitation of a medium by photons, generalized to take into account the finiteness of the velocity of excitation carriers. This approach enables us to propose a scaling that generalizes Richardson's t3 scaling law to the combined regime of Lévy flights and Lévy walks.

The illicit use of fentanyl has led to hundreds of thousands of opioid-related deaths worldwide. Therefore, the detection of fentanyl by law enforcement and recreational users is of utmost importance. However, current detection methods are expensive, time-consuming, require special storage conditions and necessitate complex instrumentation that is generally unportable and requires skilled personnel to operate. An alternative approach would be using molecularly imprinted polymers (MIPs) as the recognition component of a handheld sensor, testing strip, or color-based assay. In this work, a molecularly imprinted polymer was made by using methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA) as the functional monomer and cross-linking monomer respectively, and benzylfentanyl (Bfen) as the template. The use of benzylfentanyl is advantageous because it closely resembles the structure of fentanyl but does not have any physiological effects as a narcotic. Important studies herein determined the optimum ratio of the template:functional monomer, with subsequent evaluations of selectivity versus the commonly encountered narcotics such as heroin, cocaine, and methamphetamine. The data obtained from the HPLC analysis showed that the Bfen-MIP was successful in selectively binding the template and actual fentanyl, better than other common narcotics.

Most patients with classic Hodgkin lymphoma (cHL) are cured with combination chemotherapy, but approximately 10-20% will relapse and another 5-10% will have primary refractory disease. The treatment landscape of relapsed/refractory (R/R) cHL has evolved significantly over the past decade following the approval of brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, and the PD-1 inhibitors, nivolumab and pembrolizumab. These agents have significantly expanded options for salvage therapy prior to autologous hematopoietic cell transplantation (AHCT), post-transplant maintenance, and treatment of relapse after AHCT, which have led to improved survival in the modern era. In this review, we highlight our approach to management of R/R cHL in 2023 with a focus on choosing first salvage therapy, post-transplant maintenance, and treatment of relapse after AHCT. We also discuss management of older adults and transplant-ineligible patients who require a separate approach. Finally, we review novel immunotherapy approaches in clinical trials, including combinations of PD-1 inhibitors with other immune-activating agents as well as novel antibody-drug conjugates, bispecific antibodies, and cellular immunotherapies. Ongoing studies assessing biomarkers of response to immunotherapy and dynamic biomarkers such as circulating tumor DNA may further inform treatment decisions and enable a more personalized approach in the future.

We investigate the determinants of U.S. bilateral imports of olive oil and their dynamics from shocks in foreign supplies and changes in U.S. olive oil demand, using an augmented gravity framework that leads to an equilibrium of bilateral trade flows from olive oil exporters to the U.S. market. The empirical specification is applied at the disaggregated HS-6 level in a panel dataset, and three estimation techniques (truncated OLS, PPML, Heckman), for which the latter two account for zero trade flows, the extensive margin of trade and the potential censored distribution of exports with zero trade flows. We run Reset and HPC tests to qualify our results. On the supply side, exporters’ capacity to exports, multilateral trade resistance, and immigrants’ networks into the US are strong determinants of the bilateral trade flows for both aggregate olive oil exports and for virgin olive oil exports, On the consumer side, U.S. GDP, the import unit value, and immigrant network effects are robust determinants of bilateral flows as well for aggregate and virgin olive oil trade flows. Migrants’ stock, exporters’ GDP and population, and total exports revenues increase the probability of an exporter entering the U.S. market. We could not find robust evidence of consumer behavior being influenced by popular press measures of the emergence of Mediterranean diet and olive oil, or measures of cultural globalization of U.S. consumers.

The prevalence for chronic, non-healing skin wounds in the general population, most notably diabetic foot ulcers, venous leg ulcers and pressure ulcers, is approximately 2% and is expected to increase, driven mostly by an aging population and the steady rise in obesity and diabetes. Non-healing wounds often become infected, increasing the risk of life-threatening complications, which poses a significant socioeconomic burden. Aiming at an improved management of infected wounds, a variety of wound dressings incorporating antimicrobials (AMDs), namely polyhexanide (poly(hexamethylene biguanide); PHMB), have been introduced in the wound care market. However, many wound care professionals agree that none shows comprehensive and optimal antimicrobial activity. This manuscript summarizes and discusses studies on novel PHMB-releasing membranes (PRMs) for wound dressings, detailing their preparation, physical properties relevant in the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall effi-cacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.their preparation, physical properties relevant in the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall efficacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.

New fluorinated pentaphene derivative has been obtained as a potential precursor for fluorinated polycyclic aromatic hydrocarbons. In this work 7,7-difluoropentaphen-6(7H)-one was prepared from 1,1-difluoroanthracen-2(1H)-one via Diels-Alder reaction with o-quinodimethane generated in situ from o-bis(dibromomethyl)benzene. The structure of newly synthesized compound was confirmed by 1H, 13C, 19F NMR, IR and UV/Vis spectroscopy as well as high-resolution mass spectrometry.

Cybercrimes are becoming a bigger menace to both people and corporations. It poses a serious challenge to the modern digital world. According to a press release from 2019 Cisco and Cybersecurity Ventures, Cisco stopped seven trillion threats in 2018, or 20 billion threats every day, on behalf of its clients. According to Cybersecurity Ventures, the global cost of cybercrime will reach $6 trillion annually by 2021, which is significantly more than the annual damage caused by all natural disasters and more profitable than the global trade in all major illegal narcotics put together. Botnets are the most common and have a significant negative impact on any civilization among malware programmes. As a result, this study will explore various P2P botnet detection algorithms by outlining their essential characteristics, advantages and disadvantages, obstacles, and future research.

The transport of iron(III) from Fe(III)-Mn(II)-HCl mixed solutions through a flat-sheet supported liquid membrane is investigated, being the carrier phase of Cyanex 923 (commercially available phosphine oxide extractant) dissolved in Solvesso 100 (commercially available diluent), as a function of hydrodynamic conditions, concentration of manganese and HCl in the feed phase, and carrier concentration in the membrane phase. A transport model is derived that describes the transport mechanism, consisting of diffusion through a feed aqueous diffusion layer, a fast interfacial chemical reaction, and diffusion of the Fe(III)-Cyanex 923 complex across the membrane phase. The membrane diffusional resistance (Δm) and feed diffusional resistance (Δf) are calculated from the model, and their values are 145 s/cm and 361 s/cm, respectively. It is apparent that the transport of iron(III) is mainly controlled by diffusion through the aqueous feed boundary layer, being the thickness of this layer calculated as 2.9x10-3 cm. Since Mn(II) is not transported through the membrane phase, the present system allows to the purification of this manganese-bearing solutions.

Ultrafast chip nanocalorimetry opens up remarkable possibilities in materials science by allowing samples to be cooled and heated at extremely high rates. Due to heat transfer limitations, controlled ultrafast cooling and heating can only be achieved for tiny samples in calorimeters with a micron-thick membrane. Even if ultrafast heating can be controlled under quasi-adiabatic conditions, ultrafast controlled cooling can be performed if the calorimetric cell is located in a heat-conducting gas. It was found that the maximum possible cooling rate increases as 1/r0 with decreasing radius r0 of the hot zone of the membrane. The possibility of increasing the maximum cooling rate with decreasing r0 was successfully implemented in many experiments. In this regard, it is interesting to answer the question: what is the maximum possible cooling rate in such experiments if r0 tends to zero? Indeed, on submicron scales, the mean free path of gas molecules lmfp becomes comparable to r0, and the temperature jump that exists at the membrane/gas interface becomes significant. Considering the limitation associated with thermal resistance at the membrane/gas interface and considering the transfer of heat through the membrane, we show that the controlled cooling rate can reach billions of K/s, up to 1010 K/s.

The conformational preferences of the ester group have the potential to facilitate the large amplitude folding of long alkyl chains in the gas phase. They are monitored by Raman spectroscopy in supersonic jet expansions for the model system methyl butanoate, after establishing a quantitative relationship to quantum-chemical predictions for methyl methanoate. This requires a careful analysis of experimental details, and a simulation of the rovibrational contours for near-symmetric top molecules. The technique is shown to be complementary to microwave spectroscopy in quantifying coexisting conformations. It confirms that a C-O-C(=O)-C-C chain segment can be collapsed into a single all-trans conformation by collisional cooling, whereas alkyl chain isomerism beyond this five-membered chain largely survives the jet expansion. This sets the stage for the investigation of linear alkyl alkanoates in terms of dispersion-induced stretched-chain to hairpin transitions by Raman spectroscopy.

As the coronavirus disease 2019 (COVID-19) continues to rage worldwide, the United States has become the most affected country with more than 34.1 million total confirmed cases up to June 1, 2021. In this work, we investigate correlations between online social media and Internet search for the COVID-19 pandemic among 50 U.S. states. By collecting the state-level daily trends through both Twitter and Google Trends, we observe a high but state-different lag correlation with the number of daily confirmed cases. We further find that the predictive accuracy measured by the correlation coefficient is positively correlated to a state’s demographic, air traffic volume and GDP development. Most importantly, we show that a state’s early infection rate is negatively correlated with the lag to the previous peak in Internet search and tweeting about COVID-19, indicating that earlier collective awareness on Twitter/Google correlates with lower infection rate. Lastly, we demonstrate that correlations between online social media and search trends are sensitive to time, mainly due to the attention shifting of the public.

This work describes a method to carry out 2-D inversion of gravity data in terms of porosity and matrix density distribution using previous DC resistivity inversion results to constraint the fractional pore-water content in the rocks. The inversion is carried out using a controlled random search (CRS) algorithm for global optimization. The method was tested on synthetic data generated from a model representing a graben, and the results show that it can estimate accurate values of contrast-density and porosity. The method was also applied to gravity and dc experimental data collected in NE Portugal, showing results that agree quite well with the known geological information.

Even in the first quarter of XXI century, the presence of organic dyes in wastewaters is a normal occurrence in a series of countries, and being these compounds toxics, their removal from these waters is of a necessity. Among the separation technologies, adsorption processing appeared as one of the most widely used to reach this goal. The present work reviewed the most recent approaches (first half of 2021 year) about the use of a variety of adsorbents on the removal of, also, a variety of organic dyes of different nature.

Aging is accompanied by frontal lobe and non-dominant hemisphere recruitment that supports executive functioning, such as inhibitory control, which is crucial to all cognitive functions. Yet, the spatio-temporal sequence of processing underlying successful inhibition and how it changes with age is understudied. Thus, we assessed N200 (conflict monitoring) and P300 (response inhibition, performance evaluation) event-related potentials (ERPs) in young and healthy older adults during comparably performed successful stop-signal inhibition. We additionally interrogated the continuous spatio-temporal dynamics of N200- and P300-related activation within each group. Young adults had left hemisphere dominant N200, while older adults had overall larger amplitudes and right hemisphere dominance. N200 activation was biphasic in both groups but differed in scalp topography. P300 also differed, with larger right amplitudes in young, but bilateral amplitudes in old, with old larger than young in the left hemisphere. P300 was characterized by an early parieto-occipital peak in both groups, followed by a parietal slow wave only in older adults. A temporally similar but topographically different final wave followed in both groups that showed anterior recruitment in older adults. These findings illuminate differential age-related spatio-temporal recruitment patterns for conflict monitoring and response inhibition that are critically important for understanding age-related compensatory activation.

The novel coronavirus has presented specimen-access challenges to geoscientific researchers, including paleobiologists interested in fossil ammonoids. Ammonoid sutures are geometric patterns formed by the intersection of the septa and the shell wall, and have long been a diagnostic tool for ammonite researchers for such applications as species identification, taxonomic relationships, ontogenetic change, functional and evolutionary morphology, and other aspects of ammonoid paleobiology. Without access to specimens in museum and institutional collections, researchers must rely on previously published illustrations and photographs of ammonoid sutures. However, many of these illustrations were published decades ago without an index of scale. Suture tracings lacking a scale bar are not usable by researchers interested in applying the quantitativeness of fractal geometry to the interpretation of septal complexity. Additonally, distortion of the marginal elements of suture geometry occurs due to shell curvature near the venter and umbilicus. The revised approach described here eliminates the problem of missing scale information in fractal analysis of ammonite sutures, making use of just the lateral lobe and adjacent saddle. Our revised method’s non-requirement of a full hemisuture also facilitates comparisons among sutures within an ontogenetic sequence, or sutures from multiple ammonite taxa.

The current SARS- CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS- CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.

The ionic liquid A327H+Cl- is generated by reaction of the tertiary amine A327 (industrial mixture of tri-octil and tri-decyl amines) and hydrochloric acid solutions. Further, the extraction of Au(III) by A327H+Cl- ionic liquid under various variables, including metal and ionic liquid concentrations, has been investigated. Results indicate that A327H+AuCl4- is formed, by an exothermic (ΔHº= -3 kJ/mol) reaction, in the organic solution. Aqueous ionic strength influences the formation constants values and the specific interaction theory (SIT) is used to estimate the interaction coefficient between AuCl4- and H+. Gold (III) is stripped using thiocyanate media, and from the strip solutions, gold is precipitated as gold nanoparticles.

Root rot diseases remain a major global threat to the productivity of agricultural crops. They are usually caused by more than one type of pathogen and are thus often referred to as a root rot complex. Fungal and oomycete species are the predominant participants in the complex, while bacteria and viruses are also known to cause root rot. Incorporating genetic resistance in cultivated crops is considered as the most efficient and sustainable solution to counter root rot; however, resistance is often quantitative in nature. Several genetics studies in various crops have identified quantitative trait loci associated with resistance. With access to whole genome sequences, the identity of the genes within the reported loci is becoming available. Several of the identified genes have been implicated in pathogen response. However, it is becoming apparent that at the molecular level, each pathogen engages a unique set of proteins to either infest the host successfully or be defeated or contained in doing so. In this review, a comprehensive summary of the genes and potential mechanisms underlying resistance or susceptibility against the most investigated root rots of important agricultural crops is presented.

The fossil record is notorious for being incomplete and distorted, frequently conditioning the type of knowledge that can be extracted from it. In many cases, this often leads to issues when performing complex statistical analyses, such as classification tasks, predictive modelling, and variance analyses, such as those used in Geometric Morphometrics. Here different Generative Adversarial Network architectures are experimented with, testing the effects of sample size and domain dimensionality on model performance. For model evaluation, robust statistical methods were used. Each of the algorithms were observed to produce realistic data. Generative Adversarial Networks using different loss functions produced multidimensional synthetic data significantly equivalent to the original training data. Conditional Generative Adversarial Networks were not as successful. The methods proposed are likely to reduce the impact of sample size and bias on a number of statistical learning applications. While Generative Adversarial Networks are not the solution to all sample-size related issues, combined with other pre-processing steps these limitations may be overcome. This presents a valuable means of augmenting geometric morphometric datasets for greater predictive visualization.

Wound infections evidently appeared in times of World War I that accounted a significant mortality and morbidity rate among injured soldiers. Currently, around 11 million people worldwide require medical treatment for wound infections and 300,000 die every year due to untreated wound infection. The extensive use of antibiotics to treat wound infection leads to emerging new microbial strains that are resistant to many antibiotics. There is a growing concern on the emergence and re-emergence of drug-resistant pathogens such as multi-resistant bacterial strains. Hence, the development of new antimicrobial compounds or the modification of those that already exist to improve antibacterial activity is a high priority area of research. During the past few decades, nanotechnology has arisen with new promising technology for synthesis of nanobiomaterials. Metallic nanoparticles (NPs) are considered as new alternative treatment with superior antibacterial activity. In this study, new formulation of titanium oxide (TiO2) NPs with different sizes were synthesized and characterized. Genotoxicity, mutagenicity and antibacterial activities of TiO2 NPs against the causative agents of wound infection were investigated. Antibacterial activity of TiO2 NPs was conducted against three ATCC ® bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa. The results clearly illustrate a superior antibacterial activity of all newly formulated TiO2 NPs against the most causative agents of wound infection. Most of our TiO2 NPs showed non-genotoxic and non-mutagenic results at the maximum concentrations. Findings of this study will enhance the future of the therapeutic strategies against the resistant pathogenic strains that cause wound infections.

In automated manufacturing systems, most of the manufacturing processes including machining are automated. Automatic tool change is one of the important parameters for reducing manufacturing lead time. Ceramic cutting tools are used to machine hard materials. Ti[C,N] mixed alumina ceramic cutting tools are widely used to machine hardened steel and Stainless Steel due to its superior mechanical properties. Martensitic stainless steel has wide applications in screws, bolts, nuts and other engineering applications. Machining studies on Martensitic Stainless Steel was conducted using Ti[C,N] mixed alumina ceramic cutting tool. Tool life was evaluated using flank wear criterion. The tool life obtained from experimental machining process was taken as training dataset and test dataset for machine learning. Using the dataset obtained from experimental machining tool life model has been developed using Gradient Descent algorithm. The model was validated using co-efficient of determination. The accuracy of the machine learning model was tested using the test data and 99.83% accuracy was obtained. Tool life model based on Gradient Descent Algorithm was successfully implemented for the tool life of Ti[C,N] mixed alumina ceramic cutting tool.Keywords: keyword 1; keyword 2; keyword 3 (List three to ten pertinent keywords specific to the article; yet reasonably common within the subject discipline.)

COVID-19, caused by SARS-CoV-2, is responsible for widespread mortality and economic loss across almost 212 countries. The distribution of disease prevalence is, however, uneven and likely dependent on the range of human behavior and/or the pathogen and environmental variables. Here in this research we examined the correlation between daily and total COVID-19 case reports from Bangladesh and meteorological variables (average temperature, average humidity, and average wind speed) against one another using Spearman rank and Kendall correlation tests to highlight significant meteorological variables in relation to COVID-19. The tests revealed that both temperature and humidity had a non-significant correlation with COVID-19 transmission amid epicenter (EC) and non-epicenter (NEC) areas. However, a weak (KCC: 0.168, p < 0.05; SCC: 0.271, p < 0.05) correlation was found for temperature in ECs. Wind speed showed moderate to strong correlation in ECs with a very high statistical significance to both daily new cases [(KCC: 0.494, p < 0.01); (SCC: 0.689, p < 0.01)] and total cases [(KCC: 0.426, p < 0.01); (SCC: 0.617, p < 0.01)]. The COVID-19 transmission was found to have a weak (KCC: 0.354, p < 0.01) to moderate (SCC: 0.465, p < 0.01) correlation with daily new cases; however, a moderate (KCC: 0.497, p < 0.01) to strong (SCC: 0.712, p < 0.01) correlation with total cases was found in NECs. The results suggest that temperature and humidity have little influence on COVID-19 transmission, but wind speed may have some influence. Countries should prioritize social engineering to modify human behavior in order to combat the spread of COVID-19 and future pandemics.

Genomic analysis indicates that SARS-CoV-2 is most related to RaTG13, a beta corona virus derived from bats by 96% ¹. At present, RaTG13 is only available on the public database in the form of a genome sequence. The genome of RaTG13 (MN996532.1) was sequenced from the RNA of a bat faecal swab collected in 2013 from Yunnan, China, however the exact location is not mentioned. Since RaTG13 is one of the main supports for SARS-CoV-2 to have a natural origin, it is of utmost importance to understand the sample location. RNA dependent RNA polymerase (RdRp) sequence of RaTG13 shows that it is 100% similar to that of bat corona virus BtCoV/4991 and 98.7-98.9% similar to SARS-CoV-2 RdRp ². BtCoV/4991 was described to be a SARS-like (SL-) corona virus from bat faeces sampled in an abandoned mine from Mojiang ². Both the publications ^1,2 are authored by Dr. Zheng-li Shi (Z-L Shi), who is described as the bat woman of China ³. However, BtCoV/4991 has not been mentioned by Zhou et al 2020 ¹ where novel corona virus was first described. Based on the RdRp sequence similarities, similarities in sample collection dates, sample locations, and the fact that RaTG13 is mentioned synonymous to BtCoV/4991 on the Chinese bat database, it is predicted that RaTG13 and BtCoV/4991 originate from the same sample. The sample, bat faecal swab was collected in 2013 from an abandoned mineshaft in Mojiang by Dr. Shi and her work group. In 2012, in a Mojiang mineshaft, six mine workers suffered from atypical pneumonia and three of them died. These workers were engaged in the work of clearing debris from a mineshaft which had a lot of bats and bat faeces ^3,4. A detailed health investigation indicated that the miners suffered from atypical pneumonia mostly of the viral origin ⁴. Therefore, in the light of the present Covid-19 caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease in miners in 2012, should be noted.

Many ligands directly target adenosine receptors (ARs). Here we review the effects of noncanonical AR drugs on adenosinergic signaling. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g. ticagrelor, ethanol, cannabidiol), affecting intracellular metabolic pathways (e.g. methotrexate, nicotinamide riboside, salicylate, 5‐aminoimidazole‐4‐carboxamide riboside), or undetermined means (e.g. acupuncture). Yet other compounds bind ARs in addition to their canonical ‘on-target’ activity (e.g. mefloquine). The strength of experimental support for an adenosine-related role in a drug’s effects varies widely. AR knockout mice are the ‘gold standard’ method for investigating an AR role, but few drugs have been tested in these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments.

Mercury is a toxic metal, thus, it is an element which has more and more restrictions in its uses, but despite the above, the removal of this metal, from whatever the form in which it is encountered (zero valent metal, inorganic or organic compounds), and from different sources, is of a widespread interest. In the case of Hg(II), or Hg²⁺, the investigations about the treatment of Hg(II)-bearing liquid effluents (real or in most cases synthetic solutions) appear not to end, and from the various separation technologies, adsorption is the most popular among researchers. In this topic, and in the 2019 year, more than 100 publications had been devote to this field: Hg(II)-removal-adsorption. This work examined all of them.

On the system Au(III)-HCl-A324H⁺Cl^-, liquid-liquid extraction experiments were used to define the extraction equilibrium and the corresponding extraction constant, and the facilitated transport of this precious metal, from HCl solutions, across a flat-sheet supported liquid membrane was investigated, using the ionic liquid as carrier, as a function of hydrodynamic conditions, concentration of gold(III) (0.01-0.1 g/L), and HCl (0.5-6 M) in the feed phase, and carrier concentration (0.023-0.92 M) in the membrane. An uphill transport equation was derived considering aqueous feed boundary layer diffusion and membrane diffusion as controlling steps. The aqueous diffusional resistance (Δf) and the membrane diffusional resistance (Δm) were estimated from the proposed equation, being their values 241 s/cm an 9730 s/cm, respectively. The performance of the present carrier was compared against results yielded by other ionic liquids, and also it was investigated the influence that other metals had on gold(III) transport both from binary or quaternary solutions. Gold was finally recovered from receiving solutions as zero valent gold nanoparticles.

The transport of indium(III), from HCl solutions, across a supported liquid membrane in flat-sheet configuration was investigated, being the carrier the ionic liquid HA324H+Cl- (derived from the tertiary amine Hostarex A324 and hydrochloric acid). Different variables affecting the metal transport: hydrodynamic conditions in the source and receiving phases, metal and HCl concentrations in the source phase, and carrier concentration in the membrane phase, were investigated. Also the transport of indium(III) using carriers of various nature: ionic liquids, alcohol, ketone, phosphine oxide and phosphoric ester, was compared. The metal transport was modelled describing the transport mechanism as: diffusion across the source diffusion layer, a fast interfacial chemical reaction, and diffusion of the InCl4--carrier complex through the membrane support. Diffusional parameters for the transport of indium(III), from the experimental data and the model, were estimated.

The World economy after global crisis of 2008–2009 entered a restructuring era. It defines relevance of researches of its directions and patterns. The principles of determinism and systemic analysis are methodological basis of article. In research were used the methods of processing Big Date, as of continuous changes and the symmetric analysis of macroeconomic indicators according to databases of the IMF, WB, BIS, the Central banks and treasuries. As a result of the research it is proved that depth and globalism of recessionary processes are caused by a combination of crisis of world financial system and civilization problems. Intrinsic signs of risks in the modern economy caused by the duality of the nature of global crises have been identified. There are analyzes: the deficit of resources of the international financial institutions, a negative role of a fixed rate of Yuan, a big share of derivatives and off-balance obligations of banks, use of SPV in structures of deals, growth of debt obligations, trade wars, slowdown in the growth of the Chinese economy, aggravation of contradictions between global and national finances. The thesis is reasonable that deglobalization and dedollarization deepened this conflict, started the rollback mechanism from achievements of globalization, led to tariff wars. By means of a systematization it is proved the key directions of the restructuring of global economy: legal basis, leadership and reserve currency. On the basis of SWOT-analysis of the USA and China it was concluded that the question of leadership of one country should be excluded, but slow transition to use SDR (with a basket from 15–20 currencies) as a reserve.

The transport of indium(III), from HCl solutions, across a supported liquid membrane in flat-sheet configuration was investigated, being the carrier the ionic liquid HA324H⁺Cl^- (derived from the tertiary amine Hostarex A324 and hydrochloric acid). Different variables affecting the metal transport: hydrodynamic conditions in the source and receiving phases, metal and HCl concentrations in the source phase, and carrier concentration in the membrane phase, were investigated. Also the transport of indium(III) using carriers of various nature: ionic liquids, alcohol, ketone, phosphine oxide, etc., was compared. The metal transport was modelled describing the transport mechanism as: diffusion across the source diffusion layer, a fast interfacial chemical reaction, and diffusion of the InCl₄^--carrier complex through the membrane support. Diffusional parameters for the transport of indium(III), from the experimental data and the model, were estimated.

The present investigation deals with the adsorption of chromium(III) from alkaline media using multi-walled carbon nanotubes. The adsorption of Cr(III) has been studied under various experimental conditions: stirring speed of the aqueous solution, initial metal and adsorbent concentrations, NaOH concentration in the aqueous solution, and temperature. The rate law indicated that chromium adsorption is well represented by the particle diffusion model, whereas the adsorption process fits to the pseudo-second order kinetic model within an exothermic character. Equilibrium data fit to the Langmuir type-2 equilibrium isotherm in an spontaneous process. Chromium(III) can be eluted from metal-loaded nanotubes using acidic solutions, from which fine chromium(III) oxide pigment can be ultimately yielded.

Background: Catalase is a vital antioxidant enzyme that dismutates H₂O₂ into water and molecular oxygen. Many protocols have been developed to measure catalase enzyme activity. Spectrophotometric methods are the most common assays that used to assess catalase enzyme activity. Methods: Because the rate-limiting step during catalase enzyme activity depends upon the dissociation of hydrogen peroxide, the developed assay measures the reaction between a hydroquinone/anilinium sulfate/ammonium molybdate reagent and Unreacted Hydrogen Peroxide, which results in the production of a purple, disubstituted quinone compound with a maximum absorbance value at 550 nm. Results: To clarify the precision of the developed method, the coefficients of variation were determined to be 2.6% and 4.7% for within run measurements and between run measurements, respectively. This method returned results that correlated well (r = 0.9982) with the results returned using the peroxovanadate method to assess catalase enzyme activity. Additionally, we examined the use of the newly developed hydroquinone assay to measure catalase enzyme activity in liver and bacterial homogenate samples. Conclusion: These results demonstrated that this assay can be used for scientific research and routine health applications because it is inexpensive, simple, accurate, and rapid. This method is suitable for use in clinical pathology laboratories because it is simple and produces precise and reproducible results.

We continue our recent endeavor in which a time-dependent black hole solution of a one-loop quantum-corrected Einstein-scalar system was obtained and its near-horizon behavior was analyzed. The energy analysis led to a trans-Planckian scaling behavior near the event horizon. In the present work the analysis is extended to a rotating black hole solution of an Einstein-Maxwell-scalar system with a Higgs potential. Although the analysis becomes much more complex compared to that of the previous, we observe the same basic features, including the quantum-gravitational trans-Planckian energy near the horizon.

NIRS uses the relative absorption of light at 850nm and 760nm, to determine skeletal muscle oxygen saturation. Previous studies have used the ratio of both signals to report muscle oxygen saturation. Purpose: To evaluate the different approaches used to represent muscle oxygen saturation, and to evaluate the pulsations of the O₂heme and Heme signal. Method: Twelve participants, ages 20-29years were tested on the forearm flexor muscles using continuous wave NIRS at rest. Measurements were taken during 2-3mins rest, during physiological calibration (5-minuts Ischemia) and during reperfusion. Results: There was a significant difference in pulse size between O₂heme and Heme signal at the three locations (p < 0.05). Resting oxygen saturation was 58.8+9.2%, 69.6+3.9%, and 89.2+6.9% when calibrated using O₂heme, TSI, and Heme, respectively. Conclusion: The difference in magnitude of O₂heme and Heme pulse with each heartbeat might suggest different anatomical locations of these signals, which propose calibrating with just one of the signals instead of the ratio of both. Calculations of physiological calibration must account for increased blood volume in the tissue, because of the changes in blood volume which appear to be primarily from the O₂heme signal. Resting oxygen levels calibrated with Heme agrees with theoretical oxygen saturation.

Tight regulation of gene transcription is essential for normal development, tissue homeostasis and disease-free survival. Enhancers are distal regulatory elements in the genome that provide specificity to gene expression programs and are frequently misregulated in cancer. Recent studies examined various enhancer-driven malignant dependencies and identified different approaches to specifically target these programs. In this review, we describe numerous features that make enhancers good transcriptional targets in cancer therapy and discuss different approaches to overcome enhancer perturbation. Interestingly, a number of approved therapeutic agents such as cyclosporine, steroid hormones, and thiazolidinediones actually function by affecting enhancer landscapes by directly targeting very specific transcription factor programs. More recently, a broader approach to targeting deregulated enhancer programs has been achieved via Bromodomain and Extraterminal (BET) inhibition or perturbation of transcription-related cyclin-dependent kinases (CDK). One challenge to enhancer-targeted therapy is proper patient stratification. We suggest that monitoring of enhancer RNA (eRNA) expression may serve as a unique biomarker of enhancer activity that can help to predict and monitor responsiveness to enhancer-targeted therapies. A more thorough investigation of cancer-specific enhancers and the underlying mechanisms of deregulation will pave the road for an effective utilization of enhancer modulators in a precision oncology approach to cancer treatment.

Endocannbinoids system (ECS) engrossed a considerable interest as potential therapeutic targets in various carcinomas and cancer related conditions alongside with neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed the light over the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug-drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but the bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (glycoprotein p, breast cancer resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP- glucuronosyltransferases). The caveats should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.

Accurate repair of DNA is critical for genome stability and cancer prevention. DNA double-strand breaks are one of the most toxic lesions and can be repaired using homologous recombination (HR). HR is a high-fidelity DNA repair pathway that uses a homologous template for repair. One central HR step is RAD51 nucleoprotein filament formation on the single-stranded DNA ends, a step required for the homology search and strand invasion steps of HR. RAD51 filament formation is tightly controlled by many positive and negative regulators, collectively termed the RAD51 mediators. The RAD51 mediators function to nucleate, elongate, stabilize, and disassemble RAD51 during repair. In model organisms, RAD51 paralogs are RAD51 mediator proteins that structurally resemble RAD51 and promote its HR activity. New functions for the RAD51 paralogs during replication and in RAD51 filament flexibility have recently been uncovered. Mutations in the human RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3, and SWSAP1) are found in a subset of breast and ovarian cancers. Despite their discovery three decades ago, few advances have been made in understanding the function of the human RAD51 paralogs. Here we discuss the current perspective on the RAD51 paralogs in vivo and in vitro function and their relationship with cancer in vertebrate models.

Information-related measures are useful tools for multi-variable data analysis, as measures of dependence among variables, and as descriptions of order and disorder in biological and physical systems. Measures, like marginal entropies, mutual / interaction / multi -information, have long been used in a number of fields including descriptions of systems complexity and biological data analysis. The mathematical relationships among these measures are therefore of significant inherent interest. Relations between common information measures include the duality relations based on Möbius inversion on lattices. These are the direct consequence of the symmetries of the lattices of the sets of variables (subsets ordered by inclusion). While these relationships are of significant interest there has been, to our knowledge, no systematic examination of the full range of relationships of this diverse range of functions into a unifying formalism as we do here. In this paper we define operators on functions on these lattices based on the Möbius inversions that map functions into one another (Möbius operators). We show that these operators form a simple group isomorphic to the symmetric group S₃. Relations among the set of functions on the lattice are transparently expressed in terms of the operator algebra, and, applied to the information measures, can be used to derive a wide range of relationships among diverse information measures. The Möbius operator algebra is naturally generalized which yields extensive new relationships. This formalism now provides a fundamental unification of information-related measures, and the isomorphism of all distributive lattices with the subset lattice implies an even broader application of these results.

In this work, the parameters of plasma (electron temperature (T_e), electron density n_e, plasma frequency (f_p) , Debye length (λ_D) and Debye number (N_D)) have been studied by using the spectrometer that collect the spectrum of Laser produce Cadmium telluride plasma at different energies. The results of electron temperature for CdTe range 0.93-1.18 eV also the electron density 5 × 10¹⁰ – 3.8 × 10¹¹ cm^-3 have been measured under vacuum reaching 2.5 × 10^-2 mbar .Optical properties of CdTe were determined through the optical transmission method using ultraviolet visible spectrophotometer within the range 190 – 1100 nm.

Members of the genus Mycoplasma and related organisms impose a substantial burden of infectious diseases on humans and animals, but the last comprehensive review of mycoplasmal pathogenicity was published 20 years ago. Post-genomic analyses have now begun to support the discovery and detailed molecular biological characterization of a number of specific mycoplasmal virulence factors. This review covers three categories of defined mycoplasmal virulence effectors: 1) specific macromolecules including the superantigen MAM, the ADP-ribosylating CARDS toxin, sialidase, cytotoxic nucleases, cell-activating diacylated lipopeptides, and phosphocholine-containing glycoglycerolipids; 2) the small molecule effectors hydrogen peroxide, hydrogen sulfide, and ammonia; and 3) several putative mycoplasmal orthologs of virulence effectors documented in other bacteria. Understanding such effectors and their mechanisms of action at the molecular level connects the biology of the bacteria to direct effects on the host and host responses they elicit, and is expected to translate into new interventions for human and veterinary mycoplasmosis.

In this paper, a new anode environmentally friendly for hydrogen production was developed based on 430 stainless steel with an electrodeposited cobalt layer. The novelty of this work is the cobalt source once the electrodeposition bath was obtained from recycling of spent Li-ion batteries cathode with composition LiCoO₂. The electrodeposited cobalt behaves as supercapacitor in KOH 1M. In the linear voltammetry in KOH 1M, when the overpotential reaches 370 mV, the anodic density current for 430 SS/Co is 19 mA cm⁻². Thus, the anode developed in this paper achieves the double of density current with half of production cost if compared with 316SS. Moreover the anode construction described in this paper is an excellent option for Li- ion battery recycling.

In this paper the application of recycled Li-ion batteries spent cathode (LIB-SC) combined with NaHCO₃/H₂O₂ system is presented for the first time in the literature as an alternative for degradation of potentially toxic organic molecules. The model pollutant choice was methylene blue molecule. The spent cathode composition corresponds to LiCoO₂, which was proved by the XRD and EDX. Regarding the decolorization of methylene blue solution, the addition of NaHCO₃ in comparison with only H₂O₂ reduces the complete decolorization time in 96%. This reduction occurs because the radical CO₃ is more stable than OH. In this way, the application the system proposed in this article is aimed at solving two major global problems: the disposal of cell phone batteries and the pollution of liquid effluents.

The Aminofunctional starch/Carboxylated nitrile butadiene rubber (ANS/XNBR) latex films were prepared with control (0), 5, 10, 15, and 20 phr of ANS loadings. The films were subjected to soil burial test for 8 weeks, which recovered every two weeks to quantify the degraded properties. The control (week 0) and biodegraded films were subjected to physical tests (crosslink density, tensile, and tear strength tests) and biodegradation quantification (mass loss retention, and water vapor transmission rates). The optimum physical properties of ANS/XNBR films were subjected to further assessment of its degradation properties which include morphological (optical and scanning electron microscopes (SEM)), Fourier transform infrared (FTIR) analysis, and thermogravimetric analysis (TGA) respectively. Overall, mechanical properties of biodegraded ANS/XNBR latex films decreased as biodegradation period elapses. The biodegradation assessment via water vapor transmission rates and mass loss analyses indicates the high degree of biodegradation rates were observed with higher loading of ANS/XNBR latex films. Morphological analyses via optical microscope shows the transformation of the films surface opacity during biodegradation test. SEM images depicted the microorganism remains on the film surfaces. For FTIR analysis, the most significant changes in the spectras of the films appeared in the region of 790–3000 cm⁻¹. TGA thermograph shows the thermal retention of the materials decreased, as the biodegradation period elapses for optimum ANS/XNBR latex films. From the results obtained, ANS/XNBR latex films shows optimum degradation and mechanical properties at 10 phr filler loading.

In this work the efficiency of a new μ-mixer design is investigated. As in this type of devices the Reynolds number is low, mixing is diffusion dominated and it can be enhanced by creating secondary flows. In this study we propose the introduction of helical inserts into a straight tube to create swirling flow. The influence of the insert’s geometrical parameters (pitch and length of the propeller blades) and of the Reynolds number on the mixing efficiency and on the pressure drop are numerically investigated. The mixing efficiency of the device is assessed by calculating a number, i.e. the Index of Mixing Efficiency that quantifies the uniformity of concentration at the outlet of the device. The influence of the design parameters on the mixing efficiency is assessed by performing a series of “computational” experiments, in which the values of the parameter are selected using DOE methodology. Finally using the numerical data, appropriate design equations are formulated, which, for given values ​​of the design parameters, can estimate with reasonable accuracy both the mixing efficiency and the pressure drop of the proposed mixing device.

Recent methodological advances have enabled researchers to track the network structure of the human brain over time. Together, these studies provide novel insights into effective brain function, highlighting the importance of the systems-level perspective in understanding the manner in which the human brain organizes its activity to facilitate behavior. Here, we review a range of recent fMRI and electrophysiological studies that have mapped the relationship between inter-regional communication and network structure across a diverse range of brain states. In doing so, we identify both behavioral and biological axes that may underlie the tendency for network reconfiguration. We conclude our review by providing suggestions for future research endeavors that may help to refine our understanding of the functioning of the human brain.

Blockchain technology has become one of the most popular technologies for maintaining digital transactions. From the foundation of Bitcoin to the now predominant smart contract, blockchain technology promises to induce a shift in thought about digital transactions in many fields, such as energy, healthcare, Internet of Things, cybersecurity, financial services and the supply chain. Despite blockchain technology offers many cryptography advantages such as immutability, digital signature and hashing; it has suffered from several critical cybersecurity threats and vulnerabilities. In this paper, we build upon the previous studies on vulnerabilities and investigates over 60 real cybersecurity incidents that have been happening on the blockchain networks between 2009 and 2019. We categorise those incidents against the key cybersecurity vulnerabilities in blockchain technologies; and have developed a taxonomy that captures five types of cybersecurity threats and vulnerabilities based on five main players in blockchain. The outcome of this research prompted concerns and research direction in developing countermeasures to alleviate these risks.

Reduced-order electrothermal models play a key role in the design and control of lithium- ion cell stacks, calling for accurate model parameter calibration. This paper presents a complete electrical and thermal experimental characterization procedure for coupled modeling of cylindrical lithium-ion cells in order to implement them in a prototype Formula SAE hybrid racing car. The main 4goal of the tests is to determine cell capacity variations with temperatures and discharge currents, to predict the open circuit voltage of the cell and its entropic component. A simple approach for the characterization of the battery equivalent electrical circuit and a two-steps thermal characterization method are also shown. The investigations are carried out on four commercial 18650 NMC lithium cells. The model demonstrated to predict the battery voltage at a RMS error lower than 20mV and the temperature to a RMS error equal to 0.5 ◦C. The authors hope that this manuscript can contribute to the development of standardized characterization techniques for such cells, while offering experimental data and validated models that can be used by researchers and BMS designers in different applications.

Soil secondary salinization has seriously affected the greenhouse vegetable production in China. To improve the secondary salinization greenhouse soil and enhance the soil physical-chemical properties in an eco-environmental way, different organic amendments (straw, straw biochar, Trichoderma bio-organic manure, commercial organic manure) were applied using pot experiment for 60 day to comprehensively screen the optimal remediation method. In this study, soil nutrient condition and salt movement were assessed, and predictive models using multi-linear regression (MLR) and Random Forest (RF) were developed to estimate soil salinization parameters. The findings indicated a significant decrease in soil salt content following the application of organic materials compared to the control treatment. Specifically, the addition of straw at a rate of 250g/kg resulted in a 59.38% reduction in soil salt levels after 60 days (P < 0.05). Furthermore, the main salt ions exhibited dynamic changes over the course of the experiment, with reductions observed in Na+, Ca2+, Cl-, and NO3- content under the 250 g/kg straw treatment by 83.63%, 74.67%, 63.26%, 59.07%, respectively, compared to CK (P < 0.05). In addition, the SO42- content under 125 g/kg commercial organic manure amendment reduced by 48.94%, respectively (P < 0.05). Contrary to expectations, the addition of organic materials significantly increased the levels of total nutrients (N/P/K) and available potassium (AK) and phosphorus (AP) in the soil. Specifically, the addition of straw at a rate of 250 g/kg resulted in increases of 18.02%-87.38% in total potassium (TK), 66.67%-200% in total phosphorus (TP), and 142.87%-367.8% in AK after a period of sixty days (P < 0.05). Ultimately, the treatment involving the addition of 250 g/kg of straw demonstrated the most pronounced impact on the physical and chemical properties of the soil. The random forest method shows promise in accurately predicting soil salt and soil sodium adsorption ratio (SAR)indicators, thereby providing a valuable tool for estimating soil properties.

In this study, the olive pomace was considered because of its importance in the environment. So, this study carried out to estimate the total nitrogen content and the fatty acids profile of olive pomace. The olive pomace samples were collected from Irbid, Jarash, Ajloun and Mafraq during the harvesting season 2014 to study the biochemical characteristics of fatty acid composition and the total nitrogen (TN) content. The total nitrogen content was determined by standard Kjeldahl method and the fatty acid profile was detected by gas chromatography (GC). The results show that the total nitrogen content ranged from (0.39 ± 0.0) to (0.62 ± 0.02) with statistically significant difference suggesting that the composition of matrices and their percentage may be responsible for composition of amendments. The calculated total protein percentage ranged between (2.43 ± 0.00) to (3.87 ± 0.17). Also, 13 different fatty acids were quantitatively profiled and quantitated. Oleic acid (C 18:1) was found to be the highest percentage of all other fatty acids and ranged between (59.03%) and (63.81%), moreover the C 18:1/C 18:2 (oil quality) was calculated and C.V% showed variation meaning that nutritional implication could affect the oxidative stability of oils. In conclusion, OP by-product could give a sustainable and alternative-cheap source for fertilizers, pharmaceutical industries, cosmetics and other industries.

Mesial temporal lobe epilepsy (mTLE) is one of the most common and refractory focal epilepsy syndromes. The molecular mechanisms of TLE are not completely understood. The aim of this study was to investigate the expression and potential function of plasma exosomal miRNAs (miR-483-5p, miR-671-5p, and miR-150-3p) in a mouse mode and in temporal lobe epilepsy patients. It was found that exosomal miRNAs were differentially expressed in three phases of the mouse mode, and exosomal miRNAs were down-regulated in mTLE patients compared with healthy controls. A bioinformatics analysis showed that target genes of exosomal miRNAs were significantly involved in the apoptotic process, cell adhesion, nervous system development, neurotrophin signaling pathway, PI3K-Akt signaling pathway, and metabolic pathways. The areas under the curve of miR-483-5p and miR-150-3p were 0.8714 (sensitivity = 75.00%, specificity = 91.65%) and 0.8213 (sensitivity = 67.50%, specificity = 90.00%), respectively. More importantly, the exosomal miRNAs were significantly associated with clinical parameters. Exosomal miRNAs may have the potential to become diagnostic and therapeutic biomarkers.

Bioactive like resveratrol, epigallocatechin gallate, curcumin, and other polyphenols often target various signalling pathways, including NFκB, TGFβ, and Wnt/β-catenin in a degenerative joint disease like osteoarthritis (OA), by executing epigenetic-modifying activities. Epigenetic modu-lation can target genes of disease pathophysiology by histone modifications, promoter DNA methylation, and non-coding RNA expression, some of which are directly involved but less ex-plored in OA. OA patients often explore options that can improve the quality of their life in ad-dition to existing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Although bi-oactive and natural compounds exhibited therapeutic potential against OA, several disadvantages loom, like insolubility and poor bioavailability. Nanoformulated bioactives promise a better way to alleviate OA since they also control systemic events, including metabolic, immunological, and inflammatory responses, by modulating host gut microbiota that can regulate OA pathogenesis. Recent data suggest gut dysbiosis in OA. However, limited evidence is available on the role of bioactive as epigenetic and gut modulators in ameliorating OA. Moreover, the question of whether polyphenolic bioactive modulates gut microbial response that results in epigenetic-controlling activities of OA pathogenesis is not known. This narrative review explored the interplay of nanoformulated bioactive and host gut microbiota on chondrocyte growth, metabolism, and epigenetic alteration linked with OA progression and pathogenesis.

Bioactive like resveratrol, epigallocatechin gallate, curcumin, and other polyphenols often target various signalling pathways, including NFκB, TGFβ, and Wnt/β-catenin in osteoarthritis (OA) pathogenesis, by executing epigenetic-modifying activities. Epigenetic modulation by bioactive is gaining traction with the onset of nutrigenomics. Such modulations can target genes by histone modifications, promoter DNA methylation, and non-coding RNA expression, some of which are directly involved in disease pathophysiology but less explored in OA. OA patients often explore options that can improve the quality of their life in addition to existing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Although bioactive and natural compounds exhibited therapeutic potential against OA, several disadvantages loom over them, like insolubility and poor bioavailability. Nanoformulated bioactives promise a better way to alleviate OA since they also control systemic events, including metabolic, immunological, and inflammatory responses, by modulating host gut microbiota that can regulate OA pathogenesis. Recent data suggest gut dysbiosis in OA. However, limited evidence is available on the role of bioactive as epigenetic and gut modulators in ameliorating OA. Moreover, the question of whether polyphenolic bioactive modulates gut microbial response that results in epigenetic-controlling activities of OA pathogenesis is not known. This narrative review explored the interplay of nanoformulated bioactive and host gut microbiota on chondrocyte growth, metabolism, and epigenetic alteration linked with OA progression and pathogenesis.

Related studies have shown that mitophagy plays a role in the progression of Atherosclerosis (AS). Utilizing GSE43292, GSE100927, and GSE159677 datasets, WGCNA and differential expression analysis identified mitophagy-related module genes and DEGs1, while single-cell analysis screened DEGs2. MR analysis revealed causal AS-linked genes in DEGs1. LASSO and expression validation identified biomarkers, evaluated via ROC curves. Further analyses included GSEA, immune infiltration, ANN, regulatory networks, and drug prediction. Four candidate genes were identified through WGCNA, differential expression analysis and MR analysis. The LASSO analysis identified CD36, IL1RN, and MME as biomarkers, while the MR analysis showed that IL1RN and MME are protective factors and CD36 is a risk factor in AS. The ROC curves disclosed that the ANN model had greater diagnostic power for AS than any other biomarker. The GSEA revealed that the biomarkers were enriched in lysosomes and hematopoietic cell lineage and were significantly positively correlated with monocytes. The regulatory network construct showed that small nucleolar RNA host gene 16 regulates MME via the micro RNAs. This study identified CD36, IL1RN, and MME as biomarkers of mitophagy in AS and indicated that they could be applied in the diagnosis and treatment of this condition.